This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Calcium-containing crystal deposition diseases are a form of degenerative arthritis that affects the elderly. The prevalence and incidence of crystal-induced arthropathies are expected to increase due to our aging population in the US and increasing number of people with osteoarthritis (OA) predisposing to cartilage calcification. The two best recognized forms of calcium crystal arthropathies seen in the elderly are calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate hydroxyapatite (HA) deposition diseases (HADD) (2). These crystal deposits can often be asymptomatic or associated with chronic articular manifestations, acute episodic arthritis, "pseudogout", erosive arthritis, or periarthritis, and may contribute directly or indirectly to an exaggerated form of OA. The genes responsible for development of HA deposition disease remains unknown. The specific objective's of this proposal is to: (1) perform wide-genome scans of two large families with HA deposition disease known ad Milwaukee shoulder and (2) evaluate the role of innate immunity of HA crystal-induced inflammation and development of OA using animal model (ank mice).